This is very neatly done study. In the initial experiments, the authors showed that pre-treatment of mice with indomethacin (which suppresses PGE2 production) increased their susceptibility to systemic inflammation following endotoxin (LPS) injection.

Interestingly, when mice were also pre-treated with EP4 agonist (PGE2 receptor), it reduced systemic inflammation following LPS injection.

Moreover, beneficial effect of EP4 agonist on systemic inflammation following LPS injection was mimicked by antibiotic pre-treatment, suggesting the role of gut barrier in protection mediated by PGE2.

Finally, the authors showed that PGE2-EP4 signaling in group 3 innate lymphoid cells was necessary for IL-22 production that contributed to maintaining gut barrier function during systemic inflammation (of note, EP4 agonist had (a) no effect in IL-22KO mice and it was still active in (b) RAG KO mice that lack adaptive immune system).

In summary, this study provided additional support for innate cell-derived IL-22 as a cytokine necessary for keeping gut tissue in healthy condition.